Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker

Protze, Stephanie; Liu, Jie; Nussinovitch, Udi; Ohana, Lily; Backx, Peter H.; Gepstein, Lior; Keller, Gordon

doi:10.1038/nbt.3745

Cited by 288 publications

(309 citation statements)

References 46 publications

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“…SAN-like cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) have been used to create biological pacemaker activity in vitro and in vivo (REF 91). In another study from an independent group, iPSC-derived cardiomyocytes were delivered into dog hearts by open thoracotomy 92 .…”

Section: Biological Pacemakersmentioning

confidence: 99%

Next-generation pacemakers: from small devices to biological pacemakers

2017

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Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator. Modern pacemakers are generally reliable, and their programmability provides options for different pacing modes tailored to specific clinical needs. Advances in device technology will probably include alternative energy sources and dual-chamber leadless pacing in the not-too-distant future. Although effective, current electronic devices have limitations related to lead or generator malfunction, lack of autonomic responsiveness, undesirable interactions with strong magnetic fields, and device-related infections. Biological pacemakers, generated by somatic gene transfer, cell fusion, or cell transplantation, provide an alternative to electronic devices. Somatic reprogramming strategies, which involve transfer of genes encoding transcription factors to transform working myocardium into a surrogate sinoatrial node, are furthest along in the translational pipeline. Even as electronic pacemakers become smaller and less invasive, biological pacemakers might expand the therapeutic armamentarium for conduction system disorders.

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Section: Biological Pacemakersmentioning

confidence: 99%

Next-generation pacemakers: from small devices to biological pacemakers

2017

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“…More recently, Protze et al reported successful differentiation and enrichment of sinoatrial node-like pacemaker cells (SANLPCs) from differentiating hPSCs by using cell surface markers and an NKX2-5-reporter hPSC line 68. They found that BMP signaling specified cardiac mesoderm toward the SANLPC fate and retinoic acid signaling enhanced the pacemaker phenotype.…”

Section: Strategies For Enriching Cardiomyocytes Derived From Hpscsmentioning

confidence: 99%

Current Strategies and Challenges for Purification of Cardiomyocytes Derived from Human Pluripotent Stem Cells

Ban¹,

Bae²,

Yoon³

2017

Theranostics

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Cardiomyocytes (CMs) derived from human pluripotent stem cells (hPSCs) are considered a most promising option for cell-based cardiac repair. Hence, various protocols have been developed for differentiating hPSCs into CMs. Despite remarkable improvement in the generation of hPSC-CMs, without purification, these protocols can only generate mixed cell populations including undifferentiated hPSCs or non-CMs, which may elicit adverse outcomes. Therefore, one of the major challenges for clinical use of hPSC-CMs is the development of efficient isolation techniques that allow enrichment of hPSC-CMs. In this review, we will discuss diverse strategies that have been developed to enrich hPSC-CMs. We will describe major characteristics of individual hPSC-CM purification methods including their scientific principles, advantages, limitations, and needed improvements. Development of a comprehensive system which can enrich hPSC-CMs will be ultimately useful for cell therapy for diseased hearts, human cardiac disease modeling, cardiac toxicity screening, and cardiac tissue engineering.

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“…For instance, retinoic acid signaling has been shown to mediate the direct differentiation of atrial and ventricular CMs, 31-33 and nodal CMs seemed to result from Activin/nodal/TGF and FGF inhibition in addition to retinoic acid activation. 34 …”

Section: Pscs In Cardiac Therapymentioning

confidence: 99%

Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy

Ichimura

Shiba

2017

Circ J

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Pluripotent stem cells (PSCs) have gained interest for cell-based regenerative therapies because of their capacity to differentiate into most somatic cell types, including cardiomyocytes. Remarkable progress in the generation of PSC-derived cardiomyocytes has been made in this decade, and recent preclinical transplantation studies using various animal models have provided proof-of-principle for their use in heart regeneration. However, several obstacles preclude their effective and safe clinical application for cardiac repair, including the need for approaches that prevent tumorigenesis, arrhythmogenesis, and immune rejection. In this review, we focus on recent progress in the field of PSC-based cardiac regenerative therapy, including the remaining hurdles and potential approaches to circumventing them.

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Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker

Cited by 288 publications

References 46 publications

Next-generation pacemakers: from small devices to biological pacemakers

Next-generation pacemakers: from small devices to biological pacemakers

Current Strategies and Challenges for Purification of Cardiomyocytes Derived from Human Pluripotent Stem Cells

Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy

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